New perspectives in the treatment of obstructive sleep apnea–hypopnea syndrome

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Source: Authors." ] ] ] "textoCompleto" => "IntroductionObstructive Sleep Apnea–Hypopnea Syndrome (OSA) has been a relevant problem since the end of the 20th century in Colombia due to the rapid increase in its prevalence, both in the adult and pediatric populations.<a class="elsevierStyleCrossRefs" href="#bib0500">1,2</a> The clinical manifestations typical of this condition, and the multiple comorbidities that tend to appear in the long term, mean that the quality of life of patients with OSA may be affected considerably and it may even cause death.<a class="elsevierStyleCrossRefs" href="#bib0510">3,4</a>Diverse therapeutic alternatives have been employed that, while mitigating the symptoms and the multi-systemic alterations deriving from OSA, do not offer definitive solutions for eliminating its causes. Many of these treatments experience low adherence by the patients or lead to adverse effects in the long and/or short term.<a class="elsevierStyleCrossRefs" href="#bib0520">5–7</a> Such limitations have motivated more exhaustive studies about the pathogenesis of OSA in order to develop new treatment options from different intervention standpoints.ObjectiveTo present the most effective, recent and innovative strategies that scientific evidence proposes for the treatment of OSA based on the anatomical and physiological mechanisms involved.Materials and methodsTo carry out this review, information was collected by way of article searches in the databases PubMed, ScienceDirect, Springer, LILACS and PEDro, using the MeSH terms: sleep apnea, obstructive; airway obstruction; obesity; sleep apnea and death; cardiovascular diseases; cognitive disorders; mental disorders; kidney diseases; endocrine system disease; metabolic syndrome X; comorbidity; therapeutics; continuos positive airway pressure; mandibular advancement; hypoglossal nerve and electric stimulation. Meta-analyses, systematic reviews, clinical trials, cohort studies, and review articles published between 2005 and 2015 in English were taken into consideration. Meta-analyses and review articles with fewer than 10 primary sources; clinical trials and cohort studies with sample sizes under 10; and publications for which full online access was not available online were all excluded.ResultsWith the search strategy outlined above, initially 311 articles were found. This number was limited to 276 after language was taken into account. Later, the number dropped to 128 with the restriction to meta-analyses, systematic reviews, clinical trials, and review articles. Finally, 40 full text online texts remained that complied with the criteria regarding the number of references mentioned above. We present the results below in several sections: definition, physiopathology, neuromuscular and anatomical alterations, obesity, treatment, and conclusions.DefinitionOSA is a disorder caused by the intermittent and repetitive obstruction of the upper airway during sleep, which results in the partial (hypopnea) or complete (apnea) of airflow. As a result, arterial oxygen desaturation and transitory and subconscious micro-arousal that rupture the circadian sleep cycle are produced. This causes the sleep to be not restful and presents as daytime excessive sleepiness, the main symptom in most OSA patients. The clinical picture also includes cyclic snoring of varying intensities and pauses of apnea reported by the patients’ spouse or family members.<a class="elsevierStyleCrossRef" href="#bib0995">8</a>The American Academy of Sleep Medicine<a class="elsevierStyleCrossRef" href="#bib0540">9</a> defines “apnea” as the reduction of airflow by ≥90% during at least 10 s, and “hypopnea” as the reduction of airflow by ≥30% during at least 10s with arterial desaturation by ≥3%. The severity of OSA is determined by the Apnea–Hypopnea Index (AHI), which indicates the quantity of apneas and hypopneas recorded in the lapse of one hour of sleep.<a class="elsevierStyleCrossRefs" href="#bib0540">9,10</a>PhysiopathologyThe pharynx, a single, complex structure surrounded by numerous muscles and soft tissues, permits phonation, speaking, deglutition, and respiration. Although it is supported by osseous and cartilaginous structures at the ends, it lacks rigid support in the transverse portion, which gives it the ability to change the size of the lumen. This characteristic is essential for performing its functions, but it also predisposes it to collapse during sleep.<a class="elsevierStyleCrossRefs" href="#bib0550">11,12</a> It has been reported that the most common sites of obstruction in the upper airway are at the level of the retropalatal region, the base of the tongue, and the hypopharynx.<a class="elsevierStyleCrossRefs" href="#bib0555">12–14</a> The place and size of the collapse depend on the anatomical conformation of each subject.Neuromuscular alterationsThe permeability of the upper airway depends to a large extent on the muscular work coordinated between the Pharyngeal Dilator Muscles (PDM) and the inspiratory muscles which exert negative intraluminal pressure to allow the entry of the airflow.<a class="elsevierStyleCrossRef" href="#bib0570">15</a> The activity of the PDMs is mediated by vagal stimulation, chemoreceptors, mechanoreceptors, and baroreceptors that detect the type of change within the upper airway.<a class="elsevierStyleCrossRefs" href="#bib0555">12,16,17</a> The most important PDMs are the genioglossus (mainly phasic) and the tensor veli palatini (mainly tonic).<a class="elsevierStyleCrossRefs" href="#bib0585">18,19</a>The tensor veli palatini is responsible for stabilizing the upper airway during the respiratory cycle, while the genioglossus is the main dilator muscle of the upper airway during inhalation.<a class="elsevierStyleCrossRefs" href="#bib0580">17,18</a> At the beginning of sleep, a fall in the activity of the PDMs is seen due to a reduction in the central respiratory drive. During the N stage (non-rapid eye movement) the phasic activity increases while the tonic activity continues to decrease until R stage is reached (rapid eye movements) in which hypotonia of all skeletal musculature occurs, with the exception of the diaphragm. In patients with OSA, there is greater reduction in the muscular activity of the PDMs at the beginning of sleep (more than physiologically expected), which predisposes the airway for collapse when the R stage is reached.<a class="elsevierStyleCrossRefs" href="#bib0580">17–20</a> During wakefulness, patients with OSA do not tend to present problems with the permeability of the upper airway; on the contrary, it has been demonstrated that the activity of the PDMs is more elevated in subjects with OSA than in health subjects, this being a compensatory neuromuscular mechanism.<a class="elsevierStyleCrossRefs" href="#bib0580">17,21</a>During the apnea episode, the increase in partial pressure of carbon dioxide (PCO2) and in the breathing effort result in a stimulation of the Reticular Activating System and micro-arousals are generated to activate the contraction of the PDMs (primordially the genioglossus) to reinitiate the circulation of air through the upper airway.<a class="elsevierStyleCrossRefs" href="#bib0555">12,22</a> However, some studies report that micro-arousals are not in direct relation with the re-opening of the upper airway, since it has been seen that episodes of apnea can end via other mechanisms, such as breathing synchronizations.<a class="elsevierStyleCrossRefs" href="#bib0610">23,24</a> In some cases, the abrupt opening of the upper airway because of a micro-arousal causes hyperventilation with subsequent hypocapnia, leading to a reduction in PDM activity and a greater collapse of the upper airway.<a class="elsevierStyleCrossRefs" href="#bib0610">23,25,26</a>Anatomical alterationsIn healthy subjects, the relation of the mass of the soft tissues is disproportionately high for the space made available by the osseous structures that surround the upper airway.<a class="elsevierStyleCrossRef" href="#bib0585">18</a> Therefore, any traumatic or pathological condition implying an excess of soft tissue and/or a small bony structure will provoke a reduction in the space of the upper airway and will make it susceptible to collapse during sleep (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRefs" href="#bib0570">15,18,27–29</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>ObesityObesity represents the largest predisposing factor of OSA.<a class="elsevierStyleCrossRefs" href="#bib0550">11,30,31</a> A central distribution of fat (abdomen and neck) is more closely related to the obstruction of the upper airway than a peripheral fat distribution (thighs and hips). In 2014, Wosu et al. observed that subjects with high risk of OSA had a greater probability of general obesity (OR 9.96; CI 95%: 4.42–22.45) than of central obesity (OR 2.78; CI 95%: 1.43–5.40) suggesting a strong positive association of a high risk of OSA with obesity.<a class="elsevierStyleCrossRef" href="#bib0655">32</a> Normally, men present a central distribution pattern (android obesity) while women present a peripheral distribution pattern (gynoid obesity).<a class="elsevierStyleCrossRef" href="#bib0660">33</a> This is one of the reasons why obese men have 2–4 times more risk to develop OSA than obese women.<a class="elsevierStyleCrossRefs" href="#bib0550">11,34</a>Fat deposits in the neck reduce the transverse area of the upper airway.<a class="elsevierStyleCrossRefs" href="#bib0590">19,35</a> Those located in the thorax and the abdomen elevate the diaphragm and reduce the size and lung compliance, especially in supine position.<a class="elsevierStyleCrossRefs" href="#bib0670">35,36</a> These alterations lead to a reduction in the lung volume and capacities, particularly the functional residual capacity (FRC).<a class="elsevierStyleCrossRefs" href="#bib0590">19,35,37</a>The caliber of the upper airway depends on and varies with the volume of the lungs, increasing during inhalation and diminishing during exhalation.<a class="elsevierStyleCrossRefs" href="#bib0685">38,39</a> In patients with OSA, this relationship seems to increase.<a class="elsevierStyleCrossRef" href="#bib0685">38</a> The mechanical foundation that explains the influence of lung volume on the size of the upper airway is found in the longitudinal traction of the trachea. The caudal displacement of the carina, which occurs during inhalation, exerts a force of longitudinal traction on the trachea that is transmitted to the pharyngeal walls through their anatomical connections with the upper airway.<a class="elsevierStyleCrossRef" href="#bib0690">39</a> The decrease in the FRC induces a decrease in the traction of the trachea, which implies that, at the level of the trachea, less Pextraluminal is required to reach collapse.<a class="elsevierStyleCrossRef" href="#bib0695">40</a> In this way, in an obese subject with central fat, the quantity of adipose tissue in the neck may be sufficient to cause collapse.TreatmentCPAP (Continuous Positive Airway Pressure)CPAP is the first-line treatment for patients with moderate and severe OSA.<a class="elsevierStyleCrossRef" href="#bib0700">41</a> It consists of a pneumatic splint that provides airflow with positive pressure (above atmospheric pressure),<a class="elsevierStyleCrossRefs" href="#bib0700">41,42</a> in such a way that when the critical closing pressure increases (understood as the point of pressure in which the upper airway begins to collapse due to the increase in the pressure exerted by the tissue surrounding the oropharyngeal portion), it exceeds the upper pressure (the pressure in the nasal and nasopharyngeal portion), altering the normal relationship Pupper>Pcrit, allowing the entry of airflow through the upper airway. This is how the closure occurs<a class="elsevierStyleCrossRefs" href="#bib0555">12,19</a> (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The positive pressure provided by the CPAP reestablishes this relationship, reinitiating the opening of the upper airway.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>The efficacy of CPAP as a method for treating OSA has been confirmed, as it reduces the symptoms and risk factors associated with comorbidities.<a class="elsevierStyleCrossRefs" href="#bib0710">43–47</a> Nevertheless, many individuals exhibit low tolerance and adherence to this type of treatment.<a class="elsevierStyleCrossRef" href="#bib0735">48</a> The efficacy of CPAP results after using it for at least four hours of sleep, five nights per week,<a class="elsevierStyleCrossRef" href="#bib0740">49</a> but it has been reported that between 23% and 83% of patients use it less than this time,<a class="elsevierStyleCrossRef" href="#bib0745">50</a> and between 8% and 15% of patients to whom CPAP is prescribed do not begin treatment.<a class="elsevierStyleCrossRef" href="#bib0750">51</a>There are many predictors to determine if a subject will or will not adhere to the use of CPAP. Among these, the following stand out: the interface (type of mask), the characteristics of the patient (age, gender, marital status), the severity of the symptoms and comorbidities, the method of initiating CPAP, the secondary effects, and both psychosocial and socioeconomic factors.<a class="elsevierStyleCrossRefs" href="#bib0735">48,52</a> Therefore, diverse strategies have been implemented to increase adherence to CPAP, such as information and education programs, behavioral therapies, and prolonged accompaniment.<a class="elsevierStyleCrossRefs" href="#bib0760">53–55</a>Regarding secondary effects, studies to evaluate long-term consequences of the use of CPAP in OSA patients have not yet been conducted. Only the immediate effects, mainly related to the CPAP interface and machine have been reported: local cutaneous erosion, dry nose and mouth, conjunctivitis, upper airway irritation, runny nose, temporary deafness, headache, and insomnia.<a class="elsevierStyleCrossRefs" href="#bib0750">51,56</a> Gastric and intestinal distension may also result due to airflow into the digestive tract.<a class="elsevierStyleCrossRef" href="#bib0780">57</a>nEPAP (Nasal Expiratory Positive Airway Pressure)nEPAP is a system adapted to provide low resistance during inhalation and high resistance during exhalation through small mechanical valves placed with adhesives in each nostril.<a class="elsevierStyleCrossRef" href="#bib0785">58</a> The final expiratory phase has the greatest rate of closure of the upper airway because there is neither positive pressure nor phasic activation of the PDMs that might guarantee the permeability of the airway. The elevated expiratory resistance provided by the nasal valves generates positive pressure that reduces the risk of collapse during late inhalation.<a class="elsevierStyleCrossRefs" href="#bib0785">58,59</a>Other mechanisms of action by which nEPAP may reduce the collapsibility of the upper airway may include: inducing pulmonary hyperinflation (which increases the FRC and the longitudinal tracheal traction) or hypercapnia from hypoventilation, causing an increase in respiratory activity in the upper airway.<a class="elsevierStyleCrossRefs" href="#bib0795">60,61</a>Some studies report that nEPAP improves the subjective perception of daytime excessive sleepiness. The AHI descends by 80%, and snoring is reduced after one year of treatment.<a class="elsevierStyleCrossRefs" href="#bib0785">58,62</a> Furthermore, it appears to have greater adherence than CPAP.<a class="elsevierStyleCrossRefs" href="#bib0785">58,63,64</a>Oral pressure therapyThis method consists of an oral interface connected to a suction pump that applies continuous negative pressure to the oral cavity to pull the soft palate forward, stabilizing the tongue. The use of this device has been associated with reductions in AHI, nighttime desaturation, and daytime excessive sleepiness. At this point, the only secondary effects perceived are irritation and discomfort in the mouth and pharynx.<a class="elsevierStyleCrossRefs" href="#bib0820">65–67</a>Oral devicesThese devices constitute the main alternative for patients with mild to moderate OSA and for those who do not tolerate or adhere to CPAP. They are designed to improve the configuration of the upper airway and prevent collapse through the reposition of the jaw and tongue.<a class="elsevierStyleCrossRef" href="#bib0835">68</a> The most frequently used are mandibular advancement devices (MAD) that increase the size of the upper airway through the protrusion of the jaw during sleep. This jaw adjustment causes upper displacement of the hyoid bone, lateral displacement of the parapharyngeal fat pads, and anterior movement of the muscles of the base of the tongue. Such modifications are associated with a decrease in the Pextraluminal and increase in the neuromuscular activation of the upper airway.<a class="elsevierStyleCrossRefs" href="#bib0840">69,70</a> Through magnetic resonance and cone beam computerized tomography, it has been observed that the sites of greatest widening are the retroglossal and velopharyngeal regions.<a class="elsevierStyleCrossRefs" href="#bib0840">69,71</a>Although CPAP has been cataloged as the most effective method for the treatment of OSA, the efficacy of the MAD may come to be similar due to its greater adherence.<a class="elsevierStyleCrossRefs" href="#bib0840">69,72</a> It has been demonstrated that it is the best option for patients with the following characteristics: young people, women, patients with small necks, positional OSA, when AHI doubles in supine position,<a class="elsevierStyleCrossRef" href="#bib0675">36</a> retrognathic jaw, and low body mass index.<a class="elsevierStyleCrossRef" href="#bib0860">73</a> It may cause alterations such as temporomandibular syndrome, tooth pain and myofascial pain, excessive salivation, dryness of the oral mucous membrane, overbite, and reduction of the protrusion.<a class="elsevierStyleCrossRefs" href="#bib0860">73,74</a>Recently, a type of MAD has been in development that includes orthodontic micro-implants connected to an extra-orally anchored mask. Although its efficacy is still undetermined, this type of equipment could be used in patients with few teeth, exaggerated gag reflex, or intolerance for classic MADs.<a class="elsevierStyleCrossRef" href="#bib0870">75</a>PillarPillar is an implant used for the treatment of snoring, and of mild and moderate OSA. It consists of three pieces of polyethylene, approximately 18mm each, that are inserted in a parallel fashion in the soft palate with local anesthetic. These pieces cause a chronic inflammatory response that creates a fibrous capsule around them to add structural support, harden the soft palate, and reduce its vibration.<a class="elsevierStyleCrossRefs" href="#bib0875">76,77</a>Its use has been associated with reductions in AHI, the intensity of snoring, and the perception of daytime excessive sleepiness.<a class="elsevierStyleCrossRef" href="#bib0885">78</a> However, it is only effective when the patients do not have retropalatal obstructions.<a class="elsevierStyleCrossRef" href="#bib0890">79</a>The main advantage of this implant is that it does not require the elimination or destruction of the soft tissue of the upper airway for placement. Thus it reduces the risk of post-operative complications and other morbidities that do present in traditional surgical procedures (such as uvulopalatopharyngoplasty or tonsillectomy).<a class="elsevierStyleCrossRefs" href="#bib0895">80,81</a>Obstructive Sleep Apnea–Hypopnea Syndrome and bariatric surgeryIn patients with morbid obesity, the use of CPAP, oral devices, and upper airway surgeries are ineffective on their own for the treatment of OSA<a class="elsevierStyleCrossRef" href="#bib0905">82</a> since obesity is the main risk factor for this condition. Bariatric surgery (BS) is presented as the optimal alternative for achieving considerable weight loss in patients with a BMI≥40 and with important comorbidities, and for whom other weight-loss options have failed.<a class="elsevierStyleCrossRefs" href="#bib0910">83,84</a>There are different procedures for bariatric surgery: adjustable gastric band, gastric sleeve, gastric bypass, and biliopancreatic diversion. Evidence has demonstrated, no matter the operation performed, that bariatric surgery is coadjuvant in the treatment of OSA, effectively reducing severity in up to 75% of cases.<a class="elsevierStyleCrossRef" href="#bib0910">83</a> The remission rate for OSA two years after bariatric surgery in relation to the quantity of weight lost is up to 40%.<a class="elsevierStyleCrossRef" href="#bib0915">84</a>Bariatric surgery lessens the circumference of the neck and abdomen, causing an increase in pulmonary volumes and reductions of AHI in the supine position, improving sleep architecture, increasing oxygen saturation, and reducing CPAP requirements.<a class="elsevierStyleCrossRefs" href="#bib0920">85–87</a> At the same time, it has been seen that 40% of patients that undergo bariatric surgery continue to present residual OSA one or two years after intervention, but this occurs mainly because patients tend to suspend, of their own accord, the use of CPAP after the surgery.<a class="elsevierStyleCrossRefs" href="#bib0915">84,88</a>Night shiftNight shift is a recent device recommended only for patients with positional OSA. It consists of a small electronic monitor attached to the lower part of the neck before falling to sleep. When the user adopts the supine position, 10s later the night shift begins emitting light vibrations that progressively increase until a change in position is detected.<a class="elsevierStyleCrossRef" href="#bib0940">89</a>In studies carried out up to this point, this device has shown greater reduction in AHI and improvement of sleep architecture compared with other types of positional therapy, such as attaching a tennis ball to the neck or sleep hygiene.<a class="elsevierStyleCrossRefs" href="#bib0945">90–92</a> Its use can be combined with CPAP or any other oral device.<a class="elsevierStyleCrossRef" href="#bib0945">90</a>Electric stimulatingThis is the only “target” therapeutic strategy for the elimination of OSA and its comorbidities. It consists of the electric stimulation of the genioglossus muscle to maintain the permeability of the upper airway during sleep.The direct electric stimulation of the genioglossus via intraoral, intramuscular, or submental electrodes is able to dilate the upper airway, reduce the PCrit and increase airflow, but it only partially reduced AHI. Furthermore, it induces sense stimulation that causes constant arousals during the night, causing daytime excessive sleepiness to persist and making its long-term use difficult.<a class="elsevierStyleCrossRefs" href="#bib0960">93,94</a> To reduce these limitations and establish a more effective method, a method of electric stimulation of the hypoglossal nerve (cranial nerve responsible for innervating the genioglossus) is being implemented.The most recent system includes a programmable and implantable pulse generator (IPG), two respiration sensors, and a stimulation electrode. The sensors detect the inhalation effort of the thorax and transmit the signal to the IPG, which sends electric impulses to the hypoglossal nerve through the electrode. A software algorithm regulates the IPG in such a way that it emits stimulation only between the end of the expiratory phase and the beginning of the next expiratory phase of each respiratory cycle. Some commands of the system, like “start”, “stop”, and “pause” can be controlled with a handheld device.<a class="elsevierStyleCrossRefs" href="#bib0970">95,96</a>The electrode is generally made of platinum/iridium, has a tripolar design that distributes the current uniformly and limits contact pressure to avoid possible nerve damage.<a class="elsevierStyleCrossRefs" href="#bib0970">95–97</a> The entire system is implanted subdermally under general anesthesia. Three incisions are made: the first, at the level of the lower edge of the submandibular gland to expose the main trunk of the nerve where the electrode is placed; the second, horizontally in the fourth intercostal region, where a 5cm tunnel is opened to place the sensors; and the third, 2cm below the clavicle, where a “pocket” with the pectoralis major muscle is made for the IPG.<a class="elsevierStyleCrossRefs" href="#bib0970">95–97</a>Different studies have confirmed the efficacy of electric stimulation of the hypoglossus nerve for increasing the flow of inspired air with a resulting reduction in AHI, without sensory stimulation or associated arousals.<a class="elsevierStyleCrossRefs" href="#bib0970">95,96</a> With fluoroscopic images, it has been possible to observe the anterior displacement of the base of the tongue, opening of the retroglossal and retropalatal regions, and anterior displacement of the hyoid bone during stimulation.<a class="elsevierStyleCrossRef" href="#bib0985">98</a>Some adverse effects related to the surgical intervention and to prolonged electric stimulation include: respiratory depression, airway obstruction, infection of surgical wounds, hematomas and nerve paralysis, muscle fatigue, abrasions in soft tissue, changes in the type of fibers, and hypertrophy of the lingual musculature. All these alterations have not yet been characterized; more long-term studies are required to corroborate them.<a class="elsevierStyleCrossRef" href="#bib0990">99</a>ConclusionsThe diverse studies carried out in sleep medicine in recent years have permitted an understanding of the complexity of the physiopathological mechanisms that lead to the appearance of OSA. Thanks to this, new treatment alternatives have been developed that seek to address the heterogeneity of this condition, as observed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Although a totally effective treatment is still unavailable, the combination of several therapeutic strategies, the prevent of modifiable risk factors like obesity, and, above all, intervention by an interdisciplinary team can achieve a notable improvement in the quality of life of patients with OSA. It is hoped that advances in science and technology may offer necessary tools for continued work in different fields of knowledge in the search for a treatment protocol that is able to directly address the etiological processes of the disease in order to reduce its prevalence.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>FundingThere was no funding for the development of this document.Conflict of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:24 [ 0 => array:3 [ "identificador" => "xres785827" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec784540" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres785826" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec784541" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Objective" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Materials and methods" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Definition" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Physiopathology" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Neuromuscular alterations" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Anatomical alterations" ] 12 => array:2 [ "identificador" => "sec0045" "titulo" => "Obesity" ] 13 => array:3 [ "identificador" => "sec0050" "titulo" => "Treatment" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "CPAP (Continuous Positive Airway Pressure)" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "nEPAP (Nasal Expiratory Positive Airway Pressure)" ] ] ] 14 => array:2 [ "identificador" => "sec0065" "titulo" => "Oral pressure therapy" ] 15 => array:2 [ "identificador" => "sec0070" "titulo" => "Oral devices" ] 16 => array:2 [ "identificador" => "sec0075" "titulo" => "Pillar" ] 17 => array:2 [ "identificador" => "sec0080" "titulo" => "Obstructive Sleep Apnea–Hypopnea Syndrome and bariatric surgery" ] 18 => array:2 [ "identificador" => "sec0085" "titulo" => "Night shift" ] 19 => array:2 [ "identificador" => "sec0090" "titulo" => "Electric stimulating" ] 20 => array:2 [ "identificador" => "sec0095" "titulo" => "Conclusions" ] 21 => array:2 [ "identificador" => "sec0100" "titulo" => "Funding" ] 22 => array:2 [ "identificador" => "sec0105" "titulo" => "Conflict of interest" ] 23 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-02-02" "fechaAceptado" => "2016-06-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec784540" "palabras" => array:5 [ 0 => "Sleep apnea syndromes" 1 => "Obesity" 2 => "Comorbidity" 3 => "Therapeutics" 4 => "Airway obstruction" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec784541" "palabras" => array:5 [ 0 => "Síndromes de la apnea del sueño" 1 => "Obesidad" 2 => "Comorbilidad" 3 => "Terapéutica" 4 => "Obstrucción de las vías aéreas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionObstructive sleep apnea–hypopnea syndrome (OSA) is an increasingly prevalent disorder in the population, which seriously compromises the quality of life of sufferers. Although continuous positive airway pressure remains the most commonly used treatment modality, its poor adhesion and relative failure have provoked several studies seeking to develop more convenient and effective alternatives for treating this condition. ObjectiveTo review the most effective, recent and innovative strategies that scientific evidence suggests for the treatment of OSA from anatomical and physiological mechanisms involved. Materials and methodsA literature review was performed from items taken from PubMed, ScienceDirect, Springer, LILACS and PEDro databases, published between 2005 and 2015 in English. ResultsOSA is an intermittent and repetitive obstruction of the upper airway during sleep, caused mainly by an imbalance in respiratory muscle synergy. For treatment, the scientific literature has recently described methods such as oral devices, oral and nasal pressure therapies, Pillar, the Night Shift, bariatric surgery and stimulation of the hypoglossal nerve. ConclusionsAlthough a fully effective treatment is not yet available, a combination of strategies from an interdisciplinary perspective can enhance the quality of life of patients. It is expected that in the coming years, the scientific and technological advances will allow for the implementation of a treatment protocol that is able to directly address the etiological processes to reduce their prevalence." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Materials and methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónEl Síndrome de apnea–hipopnea obstructiva del sueño (SAHOS) es un trastorno cada vez más prevalente en la población, que compromete seriamente la calidad de vida de quienes lo padecen. Aunque la presión positiva continua en la vía aérea es la modalidad terapéutica más utilizada, su poca adherencia y relativa insuficiencia han promovido diferentes investigaciones para desarrollar nuevas alternativas de tratamiento. ObjetivoRevisar las estrategias más recientes e innovadoras que la evidencia científica propone para el tratamiento del SAHOS con base en sus mecanismos anatómicos y fisiológicos. Materiales y métodosSe realizó una revisión bibliográfica a partir de artículos en idioma inglés, tomados de las bases de datos PubMed, ScienceDirect, Springer, LILACS y PEDro, publicados entre 2005 y 2015. ResultadosEl SAHOS es la oclusión intermitente y repetitiva de la vía aérea superior durante el sueño, causada principalmente por desbalance en la sinergia muscular respiratoria. Para su tratamiento, recientemente se han descrito modalidades como los dispositivos orales, las terapias de presión, el Pillar, el Night Shift, la cirugía bariátrica y la estimulación del nervio hipogloso. ConclusionesAunque aún no se cuenta con un tratamiento totalmente eficaz, la combinación de estrategias desde una perspectiva interdisciplinar puede mejorar la calidad de vida de estos pacientes. Se espera que durante los próximos años, los avances en ciencia y tecnología permitan implementar el protocolo de tratamiento que logre abordar directamente los procesos etiológicos de la enfermedad para poder reducir su prevalencia." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Materiales y métodos" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Cortés-Reyes E, Parrado-Bermúdez K, Escobar-Córdoba F. Nuevas Perspectivas en el Tratamiento del Síndrome de Apnea-Hipopnea Obstructiva del Sueño. Rev Colomb Anestesiol. 2017;45:62–71." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 861 "Ancho" => 1524 "Tamanyo" => 79105 ] ] "descripcion" => array:1 [ "en" => "Representation of pressures in the upper airway (Starling Resistor Model). Source: Authors." ] ] 1 => array:9 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Authors." "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Osseous alterations \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Alterations in soft tissues \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="3" align="left" valign="top">Caudal displacement of the hyoid bone</td><td class="td" title="table-entry " align="left" valign="top">Macroglossia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tonsillar hypertrophy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thickening of the lateral pharyngeal walls \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Hypoplasia and/or maxillary or mandibular retrodisplacement</td><td class="td" title="table-entry " align="left" valign="top">Thickening of the velum and uvular hypertrophy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Arched palate \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">Increase in pharynx length</td><td class="td" title="table-entry " align="left" valign="top">Deviated nasal septum \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fat deposits in the neck \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1306389.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Frequent anatomical alterations in OSA." ] ] 2 => array:9 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "Source: Authors." "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Advantages \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Disadvantages \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CPAP (first-line strategy) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Effective in the treatment of OSA and its comorbidities \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Low tolerance • Low adherence • Immediate secondary effects may present in skin, eyes, nose, mouth, pharynx, stomach, intestines \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">nEPAP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Offers high resistance during expiration only. • Effective in the reduction of AHI, snoring, daytime excessive sleepiness after one year of treatment • Greater adherence than CPAP • Inexpensive \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• None reported to date \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oral pressure therapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Effective in reducing AHI, nighttime arterial oxygen desaturation, and daytime excessive sleepiness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Irritation and pain in the mouth and pharynx \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oral devices \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Reduces extraluminal pressure at the oropharyngeal level • Activate the upper airway musculature • Effectiveness similar to the CPAP due to greater adherence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Dental alterations: pain, overbite, protrusion reduction • Temporomandibular syndrome • Myofascial pain • Excessive salivation • Dryness of oral mucous membrane \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pillar \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Reduces the risk of post-operative complications and morbidities associated with interventions where upper airway soft tissue is eliminated or destroyed \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Discomfort with deglutition • Ineffective with retropalatal obstructions \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bariatric surgery \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Optimal in patients with morbid obesity that have failed in other weight reduction treatments • Resolves positional OSA • Improves sleep architecture • Reduces CPAP requirement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Residual OSA 1 to 2 years after intervention due to total suspension of CPAP. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Night Shift \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Shown to be the most effective method for positional OSA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Sleep disruption at the beginning of treatment. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="3" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Electric stimulation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">• Only treatment that attempts to eliminate OSA • Increases inspiratory airflow \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">May have secondary effects like: • Respiratory depression • Paralysis of the phrenic nerve • Muscle fatigue 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Nuevas Perspectivas en el Tratamiento del Síndrome de Apnea–Hipopnea Obstructiva del Sueño

Edgar Cortés-Reyesa,

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ecortesr@unal.edu.co

Corresponding author at: Cr. 22 No. 45 B 38 Cons. 611, Bogotá, Colombia.

, Katherine Parrado-Bermúdeza, Franklin Escobar-Córdobab,c

a Department of Human Body Movement, Institute of Clinical Research, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá, D.C., Colombia

b Department of Psychiatry, Faculty of Medicine, Universidad Nacional de Colombia, Bogotá, D.C., Colombia

c Sueño Vigilia Colombiana Foundation, Bogotá, D.C., Colombia

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information was collected by way of article searches in the databases PubMed&#44; ScienceDirect&#44; Springer&#44; LILACS and PEDro&#44; using the MeSH terms&#58; sleep apnea&#44; obstructive&#59; airway obstruction&#59; obesity&#59; sleep apnea and death&#59; cardiovascular diseases&#59; cognitive disorders&#59; mental disorders&#59; kidney diseases&#59; endocrine system disease&#59; metabolic syndrome X&#59; comorbidity&#59; therapeutics&#59; continuos positive airway pressure&#59; mandibular advancement&#59; hypoglossal nerve and electric stimulation&#46; Meta-analyses&#44; systematic reviews&#44; clinical trials&#44; cohort studies&#44; and review articles published between 2005 and 2015 in English were taken into consideration&#46; Meta-analyses and review articles with fewer than 10 primary sources&#59; clinical trials and cohort studies with sample sizes under 10&#59; and publications for which full online access was not available online were all excluded&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0025" class="elsevierStylePara elsevierViewall">With the search strategy outlined above&#44; 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arterial oxygen desaturation and transitory and subconscious micro-arousal that rupture the circadian sleep cycle are produced&#46; This causes the sleep to be not restful and presents as daytime excessive sleepiness&#44; the main symptom in most OSA patients&#46; The clinical picture also includes cyclic snoring of varying intensities and pauses of apnea reported by the patients&#8217; spouse or family members&#46;<a class="elsevierStyleCrossRef" href="#bib0995"><span class="elsevierStyleSup">8</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The American Academy of Sleep Medicine<a class="elsevierStyleCrossRef" href="#bib0540"><span class="elsevierStyleSup">9</span></a> defines &#8220;<span class="elsevierStyleItalic">apnea&#8221;</span> as the reduction of airflow by &#8805;90&#37; during at least 10 s&#44; and &#8220;<span class="elsevierStyleItalic">hypopnea&#8221;</span> as the reduction of airflow by &#8805;30&#37; during at least 10<span class="elsevierStyleHsp" style=""></span>s with arterial desaturation by &#8805;3&#37;&#46; The severity of OSA is determined by the Apnea&#8211;Hypopnea Index &#40;AHI&#41;&#44; which indicates the quantity of apneas and hypopneas recorded in the lapse of one hour of sleep&#46;<a class="elsevierStyleCrossRefs" href="#bib0540"><span class="elsevierStyleSup">9&#44;10</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Physiopathology</span><p id="par0040" class="elsevierStylePara elsevierViewall">The pharynx&#44; a single&#44; complex structure surrounded by numerous muscles and soft tissues&#44; permits phonation&#44; speaking&#44; deglutition&#44; and respiration&#46; Although it is supported by osseous and cartilaginous structures at the ends&#44; it lacks rigid support in the transverse portion&#44; which gives it the ability to change the size of the lumen&#46; This characteristic is essential for performing its functions&#44; but it also predisposes it to collapse during sleep&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">11&#44;12</span></a> It has been reported that the most common sites of obstruction in the upper airway are at the level of the retropalatal region&#44; the base of the tongue&#44; and the hypopharynx&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">12&#8211;14</span></a> The place and size of the collapse depend on the anatomical conformation of each subject&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Neuromuscular alterations</span><p id="par0045" class="elsevierStylePara elsevierViewall">The permeability of the upper airway depends to a large extent on the muscular work coordinated between the Pharyngeal Dilator Muscles &#40;PDM&#41; and the inspiratory muscles which exert negative intraluminal pressure to allow the entry of the airflow&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">15</span></a> The activity of the PDMs is mediated by vagal stimulation&#44; chemoreceptors&#44; mechanoreceptors&#44; and baroreceptors that detect the type of change within the upper airway&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">12&#44;16&#44;17</span></a> The most important PDMs are the genioglossus &#40;mainly phasic&#41; and the tensor veli palatini &#40;mainly tonic&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0585"><span class="elsevierStyleSup">18&#44;19</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The tensor veli palatini is responsible for stabilizing the upper airway during the respiratory cycle&#44; while the genioglossus is the main dilator muscle of the upper airway during inhalation&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">17&#44;18</span></a> At the beginning of sleep&#44; a fall in the activity of the PDMs is seen due to a reduction in the central respiratory drive&#46; During the N stage &#40;non-rapid eye movement&#41; the phasic activity increases while the tonic activity continues to decrease until R stage is reached &#40;rapid eye movements&#41; in which hypotonia of all skeletal musculature occurs&#44; with the exception of the diaphragm&#46; In patients with OSA&#44; there is greater reduction in the muscular activity of the PDMs at the beginning of sleep &#40;more than physiologically expected&#41;&#44; which predisposes the airway for collapse when the R stage is reached&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">17&#8211;20</span></a> During wakefulness&#44; patients with OSA do not tend to present problems with the permeability of the upper airway&#59; on the contrary&#44; it has been demonstrated that the activity of the PDMs is more elevated in subjects with OSA than in health subjects&#44; this being a compensatory neuromuscular mechanism&#46;<a class="elsevierStyleCrossRefs" href="#bib0580"><span class="elsevierStyleSup">17&#44;21</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">During the apnea episode&#44; the increase in partial pressure of carbon dioxide &#40;PCO<span class="elsevierStyleInf">2</span>&#41; and in the breathing effort result in a stimulation of the Reticular Activating System and micro-arousals are generated to activate the contraction of the PDMs &#40;primordially the genioglossus&#41; to reinitiate the circulation of air through the upper airway&#46;<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">12&#44;22</span></a> However&#44; some studies report that micro-arousals are not in direct relation with the re-opening of the upper airway&#44; since it has been seen that episodes of apnea can end via other mechanisms&#44; such as breathing synchronizations&#46;<a class="elsevierStyleCrossRefs" href="#bib0610"><span class="elsevierStyleSup">23&#44;24</span></a> In some cases&#44; the abrupt opening of the upper airway because of a micro-arousal causes hyperventilation with subsequent hypocapnia&#44; leading to a reduction in PDM activity and a greater collapse of the upper airway&#46;<a class="elsevierStyleCrossRefs" href="#bib0610"><span class="elsevierStyleSup">23&#44;25&#44;26</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Anatomical alterations</span><p id="par0060" class="elsevierStylePara elsevierViewall">In healthy subjects&#44; the relation of the mass of the soft tissues is disproportionately high for the space made available by the osseous structures that surround the upper airway&#46;<a class="elsevierStyleCrossRef" href="#bib0585"><span class="elsevierStyleSup">18</span></a> Therefore&#44; any traumatic or pathological condition implying an excess of soft tissue and&#47;or a small bony structure will provoke a reduction in the space of the upper airway and will make it susceptible to collapse during sleep &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0570"><span class="elsevierStyleSup">15&#44;18&#44;27&#8211;29</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Obesity</span><p id="par0065" class="elsevierStylePara elsevierViewall">Obesity represents the largest predisposing factor of OSA&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">11&#44;30&#44;31</span></a> A central distribution of fat &#40;abdomen and neck&#41; is more closely related to the obstruction of the upper airway than a peripheral fat distribution &#40;thighs and hips&#41;&#46; In 2014&#44; Wosu et al&#46; observed that subjects with high risk of OSA had a greater probability of general obesity &#40;OR 9&#46;96&#59; CI 95&#37;&#58; 4&#46;42&#8211;22&#46;45&#41; than of central obesity &#40;OR 2&#46;78&#59; CI 95&#37;&#58; 1&#46;43&#8211;5&#46;40&#41; suggesting a strong positive association of a high risk of OSA with obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0655"><span class="elsevierStyleSup">32</span></a> Normally&#44; men present a central distribution pattern &#40;android obesity&#41; while women present a peripheral distribution pattern &#40;gynoid obesity&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0660"><span class="elsevierStyleSup">33</span></a> This is one of the reasons why obese men have 2&#8211;4 times more risk to develop OSA than obese women&#46;<a class="elsevierStyleCrossRefs" href="#bib0550"><span class="elsevierStyleSup">11&#44;34</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">Fat deposits in the neck reduce the transverse area of the upper airway&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">19&#44;35</span></a> Those located in the thorax and the abdomen elevate the diaphragm and reduce the size and lung compliance&#44; especially in supine position&#46;<a class="elsevierStyleCrossRefs" href="#bib0670"><span class="elsevierStyleSup">35&#44;36</span></a> These alterations lead to a reduction in the lung volume and capacities&#44; particularly the functional residual capacity &#40;FRC&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0590"><span class="elsevierStyleSup">19&#44;35&#44;37</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The caliber of the upper airway depends on and varies with the volume of the lungs&#44; increasing during inhalation and diminishing during exhalation&#46;<a class="elsevierStyleCrossRefs" href="#bib0685"><span class="elsevierStyleSup">38&#44;39</span></a> In patients with OSA&#44; this relationship seems to increase&#46;<a class="elsevierStyleCrossRef" href="#bib0685"><span class="elsevierStyleSup">38</span></a> The mechanical foundation that explains the influence of lung volume on the size of the upper airway is found in the longitudinal traction of the trachea&#46; The caudal displacement of the carina&#44; which occurs during inhalation&#44; exerts a force of longitudinal traction on the trachea that is transmitted to the pharyngeal walls through their anatomical connections with the upper airway&#46;<a class="elsevierStyleCrossRef" href="#bib0690"><span class="elsevierStyleSup">39</span></a> The decrease in the FRC induces a decrease in the traction of the trachea&#44; which implies that&#44; at the level of the trachea&#44; less <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">extraluminal</span> is required to reach collapse&#46;<a class="elsevierStyleCrossRef" href="#bib0695"><span class="elsevierStyleSup">40</span></a> In this way&#44; in an obese subject with central fat&#44; the quantity of adipose tissue in the neck may be sufficient to cause collapse&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Treatment</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">CPAP &#40;Continuous Positive Airway Pressure&#41;</span><p id="par0080" class="elsevierStylePara elsevierViewall">CPAP is the first-line treatment for patients with moderate and severe OSA&#46;<a class="elsevierStyleCrossRef" href="#bib0700"><span class="elsevierStyleSup">41</span></a> It consists of a pneumatic splint that provides airflow with positive pressure &#40;above atmospheric pressure&#41;&#44;<a class="elsevierStyleCrossRefs" href="#bib0700"><span class="elsevierStyleSup">41&#44;42</span></a> in such a way that when the critical closing pressure increases &#40;understood as the point of pressure in which the upper airway begins to collapse due to the increase in the pressure exerted by the tissue surrounding the oropharyngeal portion&#41;&#44; it exceeds the upper pressure &#40;the pressure in the nasal and nasopharyngeal portion&#41;&#44; altering the normal relationship <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">upper</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">crit</span>&#44; allowing the entry of airflow through the upper airway&#46; This is how the closure occurs<a class="elsevierStyleCrossRefs" href="#bib0555"><span class="elsevierStyleSup">12&#44;19</span></a> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The positive pressure provided by the CPAP reestablishes this relationship&#44; reinitiating the opening of the upper airway&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">The efficacy of CPAP as a method for treating OSA has been confirmed&#44; as it reduces the symptoms and risk factors associated with comorbidities&#46;<a class="elsevierStyleCrossRefs" href="#bib0710"><span class="elsevierStyleSup">43&#8211;47</span></a> Nevertheless&#44; many individuals exhibit low tolerance and adherence to this type of treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0735"><span class="elsevierStyleSup">48</span></a> The efficacy of CPAP results after using it for at least four hours of sleep&#44; five nights per week&#44;<a class="elsevierStyleCrossRef" href="#bib0740"><span class="elsevierStyleSup">49</span></a> but it has been reported that between 23&#37; and 83&#37; of patients use it less than this time&#44;<a class="elsevierStyleCrossRef" href="#bib0745"><span class="elsevierStyleSup">50</span></a> and between 8&#37; and 15&#37; of patients to whom CPAP is prescribed do not begin treatment&#46;<a class="elsevierStyleCrossRef" href="#bib0750"><span class="elsevierStyleSup">51</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">There are many predictors to determine if a subject will or will not adhere to the use of CPAP&#46; Among these&#44; the following stand out&#58; the interface &#40;type of mask&#41;&#44; the characteristics of the patient &#40;age&#44; gender&#44; marital status&#41;&#44; the severity of the symptoms and comorbidities&#44; the method of initiating CPAP&#44; the secondary effects&#44; and both psychosocial and socioeconomic factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0735"><span class="elsevierStyleSup">48&#44;52</span></a> Therefore&#44; diverse strategies have been implemented to increase adherence to CPAP&#44; such as information and education programs&#44; behavioral therapies&#44; and prolonged accompaniment&#46;<a class="elsevierStyleCrossRefs" href="#bib0760"><span class="elsevierStyleSup">53&#8211;55</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Regarding secondary effects&#44; studies to evaluate long-term consequences of the use of CPAP in OSA patients have not yet been conducted&#46; Only the immediate effects&#44; mainly related to the CPAP interface and machine have been reported&#58; local cutaneous erosion&#44; dry nose and mouth&#44; conjunctivitis&#44; upper airway irritation&#44; runny nose&#44; temporary deafness&#44; headache&#44; and insomnia&#46;<a class="elsevierStyleCrossRefs" href="#bib0750"><span class="elsevierStyleSup">51&#44;56</span></a> Gastric and intestinal distension may also result due to airflow into the digestive tract&#46;<a class="elsevierStyleCrossRef" href="#bib0780"><span class="elsevierStyleSup">57</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">nEPAP &#40;Nasal Expiratory Positive Airway Pressure&#41;</span><p id="par0100" class="elsevierStylePara elsevierViewall">nEPAP is a system adapted to provide low resistance during inhalation and high resistance during exhalation through small mechanical valves placed with adhesives in each nostril&#46;<a class="elsevierStyleCrossRef" href="#bib0785"><span class="elsevierStyleSup">58</span></a> The final expiratory phase has the greatest rate of closure of the upper airway because there is neither positive pressure nor phasic activation of the PDMs that might guarantee the permeability of the airway&#46; The elevated expiratory resistance provided by the nasal valves generates positive pressure that reduces the risk of collapse during late inhalation&#46;<a class="elsevierStyleCrossRefs" href="#bib0785"><span class="elsevierStyleSup">58&#44;59</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Other mechanisms of action by which nEPAP may reduce the collapsibility of the upper airway may include&#58; inducing pulmonary hyperinflation &#40;which increases the FRC and the longitudinal tracheal traction&#41; or hypercapnia from hypoventilation&#44; causing an increase in respiratory activity in the upper airway&#46;<a class="elsevierStyleCrossRefs" href="#bib0795"><span class="elsevierStyleSup">60&#44;61</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Some studies report that nEPAP improves the subjective perception of daytime excessive sleepiness&#46; The AHI descends by 80&#37;&#44; and snoring is reduced after one year of treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0785"><span class="elsevierStyleSup">58&#44;62</span></a> Furthermore&#44; it appears to have greater adherence than CPAP&#46;<a class="elsevierStyleCrossRefs" href="#bib0785"><span class="elsevierStyleSup">58&#44;63&#44;64</span></a></p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Oral pressure therapy</span><p id="par0115" class="elsevierStylePara elsevierViewall">This method consists of an oral interface connected to a suction pump that applies continuous negative pressure to the oral cavity to pull the soft palate forward&#44; stabilizing the tongue&#46; The use of this device has been associated with reductions in AHI&#44; nighttime desaturation&#44; and daytime excessive sleepiness&#46; At this point&#44; the only secondary effects perceived are irritation and discomfort in the mouth and pharynx&#46;<a class="elsevierStyleCrossRefs" href="#bib0820"><span class="elsevierStyleSup">65&#8211;67</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Oral devices</span><p id="par0120" class="elsevierStylePara elsevierViewall">These devices constitute the main alternative for patients with mild to moderate OSA and for those who do not tolerate or adhere to CPAP&#46; They are designed to improve the configuration of the upper airway and prevent collapse through the reposition of the jaw and tongue&#46;<a class="elsevierStyleCrossRef" href="#bib0835"><span class="elsevierStyleSup">68</span></a> The most frequently used are mandibular advancement devices &#40;MAD&#41; that increase the size of the upper airway through the protrusion of the jaw during sleep&#46; This jaw adjustment causes upper displacement of the hyoid bone&#44; lateral displacement of the parapharyngeal fat pads&#44; and anterior movement of the muscles of the base of the tongue&#46; Such modifications are associated with a decrease in the <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">extraluminal</span> and increase in the neuromuscular activation of the upper airway&#46;<a class="elsevierStyleCrossRefs" href="#bib0840"><span class="elsevierStyleSup">69&#44;70</span></a> Through magnetic resonance and cone beam computerized tomography&#44; it has been observed that the sites of greatest widening are the retroglossal and velopharyngeal regions&#46;<a class="elsevierStyleCrossRefs" href="#bib0840"><span class="elsevierStyleSup">69&#44;71</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Although CPAP has been cataloged as the most effective method for the treatment of OSA&#44; the efficacy of the MAD may come to be similar due to its greater adherence&#46;<a class="elsevierStyleCrossRefs" href="#bib0840"><span class="elsevierStyleSup">69&#44;72</span></a> It has been demonstrated that it is the best option for patients with the following characteristics&#58; young people&#44; women&#44; patients with small necks&#44; positional OSA&#44; when AHI doubles in supine position&#44;<a class="elsevierStyleCrossRef" href="#bib0675"><span class="elsevierStyleSup">36</span></a> retrognathic jaw&#44; and low body mass index&#46;<a class="elsevierStyleCrossRef" href="#bib0860"><span class="elsevierStyleSup">73</span></a> It may cause alterations such as temporomandibular syndrome&#44; tooth pain and myofascial pain&#44; excessive salivation&#44; dryness of the oral mucous membrane&#44; overbite&#44; and reduction of the protrusion&#46;<a class="elsevierStyleCrossRefs" href="#bib0860"><span class="elsevierStyleSup">73&#44;74</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Recently&#44; a type of MAD has been in development that includes orthodontic micro-implants connected to an extra-orally anchored mask&#46; Although its efficacy is still undetermined&#44; this type of equipment could be used in patients with few teeth&#44; exaggerated gag reflex&#44; or intolerance for classic MADs&#46;<a class="elsevierStyleCrossRef" href="#bib0870"><span class="elsevierStyleSup">75</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Pillar</span><p id="par0135" class="elsevierStylePara elsevierViewall">Pillar is an implant used for the treatment of snoring&#44; and of mild and moderate OSA&#46; It consists of three pieces of polyethylene&#44; approximately 18<span class="elsevierStyleHsp" style=""></span>mm each&#44; that are inserted in a parallel fashion in the soft palate with local anesthetic&#46; These pieces cause a chronic inflammatory response that creates a fibrous capsule around them to add structural support&#44; harden the soft palate&#44; and reduce its vibration&#46;<a class="elsevierStyleCrossRefs" href="#bib0875"><span class="elsevierStyleSup">76&#44;77</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Its use has been associated with reductions in AHI&#44; the intensity of snoring&#44; and the perception of daytime excessive sleepiness&#46;<a class="elsevierStyleCrossRef" href="#bib0885"><span class="elsevierStyleSup">78</span></a> However&#44; it is only effective when the patients do not have retropalatal obstructions&#46;<a class="elsevierStyleCrossRef" href="#bib0890"><span class="elsevierStyleSup">79</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">The main advantage of this implant is that it does not require the elimination or destruction of the soft tissue of the upper airway for placement&#46; Thus it reduces the risk of post-operative complications and other morbidities that do present in traditional surgical procedures &#40;such as uvulopalatopharyngoplasty or tonsillectomy&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0895"><span class="elsevierStyleSup">80&#44;81</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Obstructive Sleep Apnea&#8211;Hypopnea Syndrome and bariatric surgery</span><p id="par0150" class="elsevierStylePara elsevierViewall">In patients with morbid obesity&#44; the use of CPAP&#44; oral devices&#44; and upper airway surgeries are ineffective on their own for the treatment of OSA<a class="elsevierStyleCrossRef" href="#bib0905"><span class="elsevierStyleSup">82</span></a> since obesity is the main risk factor for this condition&#46; Bariatric surgery &#40;BS&#41; is presented as the optimal alternative for achieving considerable weight loss in patients with a BMI<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>40 and with important comorbidities&#44; and for whom other weight-loss options have failed&#46;<a class="elsevierStyleCrossRefs" href="#bib0910"><span class="elsevierStyleSup">83&#44;84</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">There are different procedures for bariatric surgery&#58; adjustable gastric band&#44; gastric sleeve&#44; gastric bypass&#44; and biliopancreatic diversion&#46; Evidence has demonstrated&#44; no matter the operation performed&#44; that bariatric surgery is coadjuvant in the treatment of OSA&#44; effectively reducing severity in up to 75&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0910"><span class="elsevierStyleSup">83</span></a> The remission rate for OSA two years after bariatric surgery in relation to the quantity of weight lost is up to 40&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0915"><span class="elsevierStyleSup">84</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Bariatric surgery lessens the circumference of the neck and abdomen&#44; causing an increase in pulmonary volumes and reductions of AHI in the supine position&#44; improving sleep architecture&#44; increasing oxygen saturation&#44; and reducing CPAP requirements&#46;<a class="elsevierStyleCrossRefs" href="#bib0920"><span class="elsevierStyleSup">85&#8211;87</span></a> At the same time&#44; it has been seen that 40&#37; of patients that undergo bariatric surgery continue to present residual OSA one or two years after intervention&#44; but this occurs mainly because patients tend to suspend&#44; of their own accord&#44; the use of CPAP after the surgery&#46;<a class="elsevierStyleCrossRefs" href="#bib0915"><span class="elsevierStyleSup">84&#44;88</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Night shift</span><p id="par0165" class="elsevierStylePara elsevierViewall">Night shift is a recent device recommended only for patients with positional OSA&#46; It consists of a small electronic monitor attached to the lower part of the neck before falling to sleep&#46; When the user adopts the supine position&#44; 10<span class="elsevierStyleHsp" style=""></span>s later the night shift begins emitting light vibrations that progressively increase until a change in position is detected&#46;<a class="elsevierStyleCrossRef" href="#bib0940"><span class="elsevierStyleSup">89</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">In studies carried out up to this point&#44; this device has shown greater reduction in AHI and improvement of sleep architecture compared with other types of positional therapy&#44; such as attaching a tennis ball to the neck or sleep hygiene&#46;<a class="elsevierStyleCrossRefs" href="#bib0945"><span class="elsevierStyleSup">90&#8211;92</span></a> Its use can be combined with CPAP or any other oral device&#46;<a class="elsevierStyleCrossRef" href="#bib0945"><span class="elsevierStyleSup">90</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Electric stimulating</span><p id="par0175" class="elsevierStylePara elsevierViewall">This is the only &#8220;target&#8221; therapeutic strategy for the elimination of OSA and its comorbidities&#46; It consists of the electric stimulation of the genioglossus muscle to maintain the permeability of the upper airway during sleep&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">The direct electric stimulation of the genioglossus via intraoral&#44; intramuscular&#44; or submental electrodes is able to dilate the upper airway&#44; reduce the <span class="elsevierStyleItalic">P</span><span class="elsevierStyleInf">Crit</span> and increase airflow&#44; but it only partially reduced AHI&#46; Furthermore&#44; it induces sense stimulation that causes constant arousals during the night&#44; causing daytime excessive sleepiness to persist and making its long-term use difficult&#46;<a class="elsevierStyleCrossRefs" href="#bib0960"><span class="elsevierStyleSup">93&#44;94</span></a> To reduce these limitations and establish a more effective method&#44; a method of electric stimulation of the hypoglossal nerve &#40;cranial nerve responsible for innervating the genioglossus&#41; is being implemented&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">The most recent system includes a programmable and implantable pulse generator &#40;IPG&#41;&#44; two respiration sensors&#44; and a stimulation electrode&#46; The sensors detect the inhalation effort of the thorax and transmit the signal to the IPG&#44; which sends electric impulses to the hypoglossal nerve through the electrode&#46; A software algorithm regulates the IPG in such a way that it emits stimulation only between the end of the expiratory phase and the beginning of the next expiratory phase of each respiratory cycle&#46; Some commands of the system&#44; like &#8220;start&#8221;&#44; &#8220;stop&#8221;&#44; and &#8220;pause&#8221; can be controlled with a handheld device&#46;<a class="elsevierStyleCrossRefs" href="#bib0970"><span class="elsevierStyleSup">95&#44;96</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The electrode is generally made of platinum&#47;iridium&#44; has a tripolar design that distributes the current uniformly and limits contact pressure to avoid possible nerve damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0970"><span class="elsevierStyleSup">95&#8211;97</span></a> The entire system is implanted subdermally under general anesthesia&#46; Three incisions are made&#58; the first&#44; at the level of the lower edge of the submandibular gland to expose the main trunk of the nerve where the electrode is placed&#59; the second&#44; horizontally in the fourth intercostal region&#44; where a 5<span class="elsevierStyleHsp" style=""></span>cm tunnel is opened to place the sensors&#59; and the third&#44; 2<span class="elsevierStyleHsp" style=""></span>cm below the clavicle&#44; where a &#8220;pocket&#8221; with the pectoralis major muscle is made for the IPG&#46;<a class="elsevierStyleCrossRefs" href="#bib0970"><span class="elsevierStyleSup">95&#8211;97</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Different studies have confirmed the efficacy of electric stimulation of the hypoglossus nerve for increasing the flow of inspired air with a resulting reduction in AHI&#44; without sensory stimulation or associated arousals&#46;<a class="elsevierStyleCrossRefs" href="#bib0970"><span class="elsevierStyleSup">95&#44;96</span></a> With fluoroscopic images&#44; it has been possible to observe the anterior displacement of the base of the tongue&#44; opening of the retroglossal and retropalatal regions&#44; and anterior displacement of the hyoid bone during stimulation&#46;<a class="elsevierStyleCrossRef" href="#bib0985"><span class="elsevierStyleSup">98</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">Some adverse effects related to the surgical intervention and to prolonged electric stimulation include&#58; respiratory depression&#44; airway obstruction&#44; infection of surgical wounds&#44; hematomas and nerve paralysis&#44; muscle fatigue&#44; abrasions in soft tissue&#44; changes in the type of fibers&#44; and hypertrophy of the lingual musculature&#46; All these alterations have not yet been characterized&#59; more long-term studies are required to corroborate them&#46;<a class="elsevierStyleCrossRef" href="#bib0990"><span class="elsevierStyleSup">99</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Conclusions</span><p id="par0205" class="elsevierStylePara elsevierViewall">The diverse studies carried out in sleep medicine in recent years have permitted an understanding of the complexity of the physiopathological mechanisms that lead to the appearance of OSA&#46; Thanks to this&#44; new treatment alternatives have been developed that seek to address the heterogeneity of this condition&#44; as observed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; Although a totally effective treatment is still unavailable&#44; the combination of several therapeutic strategies&#44; the prevent of modifiable risk factors like obesity&#44; and&#44; above all&#44; intervention by an interdisciplinary team can achieve a notable improvement in the quality of life of patients with OSA&#46; It is hoped that advances in science and technology may offer necessary tools for continued work in different fields of knowledge in the search for a treatment protocol that is able to directly address the etiological processes of the disease in order to reduce its prevalence&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Funding</span><p id="par0210" class="elsevierStylePara elsevierViewall">There was no funding for the development of this document&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conflict of interest</span><p id="par0215" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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          "titulo" => "Neuromuscular alterations"
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          "titulo" => "Obesity"
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          "titulo" => "Treatment"
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              "identificador" => "sec0055"
              "titulo" => "CPAP &#40;Continuous Positive Airway Pressure&#41;"
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              "titulo" => "nEPAP &#40;Nasal Expiratory Positive Airway Pressure&#41;"
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          "titulo" => "Oral pressure therapy"
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          "identificador" => "sec0075"
          "titulo" => "Pillar"
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          "titulo" => "Obstructive Sleep Apnea&#8211;Hypopnea Syndrome and bariatric surgery"
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          "titulo" => "Night shift"
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    "fechaRecibido" => "2016-02-02"
    "fechaAceptado" => "2016-06-21"
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          "clase" => "keyword"
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          "palabras" => array:5 [
            0 => "Sleep apnea syndromes"
            1 => "Obesity"
            2 => "Comorbidity"
            3 => "Therapeutics"
            4 => "Airway obstruction"
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          "palabras" => array:5 [
            0 => "S&#237;ndromes de la apnea del sue&#241;o"
            1 => "Obesidad"
            2 => "Comorbilidad"
            3 => "Terap&#233;utica"
            4 => "Obstrucci&#243;n de las v&#237;as a&#233;reas"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Obstructive sleep apnea&#8211;hypopnea syndrome &#40;OSA&#41; is an increasingly prevalent disorder in the population&#44; which seriously compromises the quality of life of sufferers&#46; Although continuous positive airway pressure remains the most commonly used treatment modality&#44; its poor adhesion and relative failure have provoked several studies seeking to develop more convenient and effective alternatives for treating this condition&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To review the most effective&#44; recent and innovative strategies that scientific evidence suggests for the treatment of OSA from anatomical and physiological mechanisms involved&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Materials and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A literature review was performed from items taken from PubMed&#44; ScienceDirect&#44; Springer&#44; LILACS and PEDro databases&#44; published between 2005 and 2015 in English&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">OSA is an intermittent and repetitive obstruction of the upper airway during sleep&#44; caused mainly by an imbalance in respiratory muscle synergy&#46; For treatment&#44; the scientific literature has recently described methods such as oral devices&#44; oral and nasal pressure therapies&#44; Pillar&#44; the Night Shift&#44; bariatric surgery and stimulation of the hypoglossal nerve&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Although a fully effective treatment is not yet available&#44; a combination of strategies from an interdisciplinary perspective can enhance the quality of life of patients&#46; It is expected that in the coming years&#44; the scientific and technological advances will allow for the implementation of a treatment protocol that is able to directly address the etiological processes to reduce their prevalence&#46;</p></span>"
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          1 => array:2 [
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          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Materials and methods"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El S&#237;ndrome de apnea&#8211;hipopnea obstructiva del sue&#241;o &#40;SAHOS&#41; es un trastorno cada vez m&#225;s prevalente en la poblaci&#243;n&#44; que compromete seriamente la calidad de vida de quienes lo padecen&#46; Aunque la presi&#243;n positiva continua en la v&#237;a a&#233;rea es la modalidad terap&#233;utica m&#225;s utilizada&#44; su poca adherencia y relativa insuficiencia han promovido diferentes investigaciones para desarrollar nuevas alternativas de tratamiento&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Revisar las estrategias m&#225;s recientes e innovadoras que la evidencia cient&#237;fica propone para el tratamiento del SAHOS con base en sus mecanismos anat&#243;micos y fisiol&#243;gicos&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Materiales y m&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se realiz&#243; una revisi&#243;n bibliogr&#225;fica a partir de art&#237;culos en idioma ingl&#233;s&#44; tomados de las bases de datos PubMed&#44; ScienceDirect&#44; Springer&#44; LILACS y PEDro&#44; publicados entre 2005 y 2015&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El SAHOS es la oclusi&#243;n intermitente y repetitiva de la v&#237;a a&#233;rea superior durante el sue&#241;o&#44; causada principalmente por desbalance en la sinergia muscular respiratoria&#46; Para su tratamiento&#44; recientemente se han descrito modalidades como los dispositivos orales&#44; las terapias de presi&#243;n&#44; el Pillar&#44; el Night Shift&#44; la cirug&#237;a bari&#225;trica y la estimulaci&#243;n del nervio hipogloso&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Aunque a&#250;n no se cuenta con un tratamiento totalmente eficaz&#44; la combinaci&#243;n de estrategias desde una perspectiva interdisciplinar puede mejorar la calidad de vida de estos pacientes&#46; Se espera que durante los pr&#243;ximos a&#241;os&#44; los avances en ciencia y tecnolog&#237;a permitan implementar el protocolo de tratamiento que logre abordar directamente los procesos etiol&#243;gicos de la enfermedad para poder reducir su prevalencia&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Cort&#233;s-Reyes E&#44; Parrado-Berm&#250;dez K&#44; Escobar-C&#243;rdoba F&#46; Nuevas Perspectivas en el Tratamiento del S&#237;ndrome de Apnea-Hipopnea Obstructiva del Sue&#241;o&#46; Rev Colomb Anestesiol&#46; 2017&#59;45&#58;62&#8211;71&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Osseous alterations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Alterations in soft tissues&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">Caudal displacement of the hyoid bone</td><td class="td" title="table-entry  " align="left" valign="top">Macroglossia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tonsillar hypertrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Thickening of the lateral pharyngeal walls&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Hypoplasia and&#47;or maxillary or mandibular retrodisplacement</td><td class="td" title="table-entry  " align="left" valign="top">Thickening of the velum and uvular hypertrophy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Arched palate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="top">Increase in pharynx length</td><td class="td" title="table-entry  " align="left" valign="top">Deviated nasal septum&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Fat deposits in the neck&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Treatment&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Advantages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Disadvantages&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CPAP &#40;first-line strategy&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Effective in the treatment of OSA and its comorbidities&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Low tolerance<br>&#8226; Low adherence<br>&#8226; Immediate secondary effects may present in skin&#44; eyes&#44; nose&#44; mouth&#44; pharynx&#44; stomach&#44; intestines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">nEPAP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Offers high resistance during expiration only&#46;<br>&#8226; Effective in the reduction of AHI&#44; snoring&#44; daytime excessive sleepiness after one year of treatment<br>&#8226; Greater adherence than CPAP<br>&#8226; Inexpensive&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; None reported to date&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oral pressure therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Effective in reducing AHI&#44; nighttime arterial oxygen desaturation&#44; and daytime excessive sleepiness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Irritation and pain in the mouth and pharynx&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Oral devices&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Reduces extraluminal pressure at the oropharyngeal level<br>&#8226; Activate the upper airway musculature<br>&#8226; Effectiveness similar to the CPAP due to greater adherence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Dental alterations&#58; pain&#44; overbite&#44; protrusion reduction<br>&#8226; Temporomandibular syndrome<br>&#8226; Myofascial pain<br>&#8226; Excessive salivation<br>&#8226; Dryness of oral mucous membrane&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pillar&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Reduces the risk of post-operative complications and morbidities associated with interventions where upper airway soft tissue is eliminated or destroyed&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Discomfort with deglutition<br>&#8226; Ineffective with retropalatal obstructions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bariatric surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Optimal in patients with morbid obesity that have failed in other weight reduction treatments<br>&#8226; Resolves positional OSA<br>&#8226; Improves sleep architecture<br>&#8226; Reduces CPAP requirement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Residual OSA 1 to 2 years after intervention due to total suspension of CPAP&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Night Shift&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Shown to be the most effective method for positional OSA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Sleep disruption at the beginning of treatment&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="3" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Electric stimulation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8226; Only treatment that attempts to eliminate OSA<br>&#8226; Increases inspiratory airflow&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">May have secondary effects like&#58;<br>&#8226; Respiratory depression<br>&#8226; Paralysis of the phrenic nerve<br>&#8226; Muscle fatigue<br>&#8226; Changes in the type of muscle fiber<br>&#8226; Soft tissue abrasions<br>&#8226; Hypertrophy of lingual musculature&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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Article information

ISSN: 22562087
Original language: English

DOI:10.1016/j.rcae.2016.07.002

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Year/Month	Html	Pdf	Total

2024 November	10	1	11
2024 October	45	6	51
2024 September	59	13	72
2024 August	28	3	31
2024 July	33	6	39
2024 June	29	7	36
2024 May	58	2	60
2024 April	23	4	27
2024 March	41	7	48
2024 February	40	15	55
2024 January	36	5	41
2023 December	53	13	66
2023 November	45	12	57
2023 October	31	10	41
2023 September	25	6	31
2023 August	36	10	46
2023 July	26	5	31
2023 June	39	5	44
2023 May	80	4	84
2023 April	91	2	93
2023 March	62	7	69
2023 February	58	7	65
2023 January	44	6	50
2022 December	45	2	47
2022 November	40	9	49
2022 October	31	9	40
2022 September	48	6	54
2022 August	32	15	47
2022 July	20	10	30
2022 June	26	21	47
2022 May	26	6	32
2022 April	23	12	35
2022 March	36	13	49
2022 February	32	4	36
2022 January	57	9	66
2021 December	35	6	41
2021 November	25	10	35
2021 October	48	16	64
2021 September	34	7	41
2021 August	47	5	52
2021 July	12	8	20
2021 June	21	10	31
2021 May	49	9	58
2021 April	127	16	143
2021 March	65	10	75
2021 February	44	19	63
2021 January	57	14	71
2020 December	30	5	35
2020 November	41	7	48
2020 October	7	7	14
2020 September	22	5	27
2020 August	25	11	36
2020 July	11	8	19
2020 June	11	7	18
2020 May	18	6	24
2020 April	8	2	10
2020 March	16	3	19
2020 February	12	3	15
2020 January	10	3	13
2019 December	9	7	16
2019 November	3	1	4
2019 October	6	2	8
2019 September	1	0	1
2019 July	0	3	3
2019 June	1	2	3
2019 May	2	8	10
2019 January	1	0	1
2018 September	1	0	1
2018 June	8	3	11
2018 May	60	8	68
2018 April	54	13	67
2018 March	56	11	67
2018 February	27	16	43
2018 January	51	13	64
2017 December	19	18	37
2017 November	35	9	44
2017 October	45	11	56
2017 September	40	19	59
2017 August	18	8	26
2017 July	28	12	40
2017 June	49	14	63
2017 May	48	12	60
2017 April	78	18	96
2017 March	61	11	72
2017 February	31	7	38
2017 January	43	13	56
2016 December	12	15	27
2016 November	8	11	19
2016 October	13	17	30
2016 September	8	5	13
2016 August	4	3	7

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